This invention relates to methods for detecting specific telomerase-associated RNA, those being telomerase RNA template (hTR) RNA and telomerase reverse transcriptase protein (hTERT) RNA, in bodily fluids including but not limited to plasma and serum.
Ribonucleic acid (RNA) is essential to the processes that allow translation of the genetic code to form proteins necessary for cellular functions, both in normal and neoplastic cells. While the genetic code structurally exists as deoxyribonucleic acid (DNA), it is the function of RNA to carry and translate this code to the cellular sites of protein production. The pathogenesis and regulation of cancer is dependent upon RNA-mediated translation of specific genetic codes to produce proteins involved with cell proliferation, regulation, and death, including but not limited to those RNA associated with specific cellular processes characteristic of cancer, such as processes associated with cellular longevity. Furthermore, some RNA and their translated proteins, although not necessarily involved in specific neoplastic pathogenesis or regulation, may serve to delineate recognizable characteristics of particular neoplasms by either being elevated or inappropriately expressed. The RNA associated with cancer and premalignant or neoplastic states have been referred to herein as tumor-derived, or tumor-associated RNA. The invention, as described in U.S. patent application Ser. No. 09/155,152, incorporated by reference herein in its entirety, provides a method by which tumor-associated or tumor-derived RNA in bodily fluids such as plasma and serum can be detected and thus utilized for the detection, monitoring, or evaluation of cancer or premalignant conditions. One group of tumor-associated or tumor-derived RNA are telomerase-associated RNA, comprising those RNA associated with the protein and nucleic acid components of telomerase.
Telomerase is a ribonucleoprotein enzyme which plays a role in stabilizing telomere length during cell replication. While most normal cells have low levels of telomerase activity, it has been shown that most cancer cells have high levels of telomerase activity (Hiyama, 1996; Sommerfeld, 1996). The telomerase ribonucleoprotein is thus a tumor-associated protein that can be considered a marker for cancer (Califano, 1996; Suchara, 1997). The telomerase ribonucleoprotein consists of components or subunits, two of these being telomerase RNA template (hTR), and telomerase reverse transcriptase protein (hTERT)(Meyerson, 1997; Nakamura, 1997).
U.S. patent application Ser. No. 09/155,152, the entire disclosure of which is herein incorporated by reference, taught detection of telomerase-associated RNA in blood and other bodily fluids. The present invention describes a method of evaluating for two specific telomerase-associated RNA, hTR RNA and hTERT RNA, by detecting hTR mRNA or hTERT mRNA in blood, particularly plasma and serum, and other bodily fluids including but not limited to urine, effusions, ascites, saliva, cerebrospinal fluid, cervical, vaginal, and endometrial secretions, gastrointestinal secretions, bronchial secretions including sputum, and breast fluid.